Method of preparing nitromalonaldehyde and salts thereof



Patented Aug. 12, 1952 UNITED j STATES PATENT? O FFICE r Manson oF PREPARING NITROMALoNAL DEHYDE AND SALTS THEREOF v p Erwin Kuh, New Brunswick, and Hugh W.

' Stewart, Plainfield, N. J., assignors to Ameri--' can. Cyanamid Company, New York, N. Y., a

corporationof Maine No Drawing. Application May 27, 1950,

Serial No. 164,852

This inventionrelates to a new method for the preparation of nitromalonaldehyde and salts thereof.

In the past nitromalonaldehyde has been prepared exclusively from alpha,beta-dibromo-betaformylacrylic acid (mucobromic acid). Substitution for the latter of the commercially available alpha,beta-dichloro-beta-formylacrylic acid (mucochloric acid) results in the formation of very little if any nitromalonaldehyde. Mucobromic acid, although producing good yields of nitromalonaldehyde, it itself expensive to prepare, since it requires mol equivalents of expensive bromine (and only one equivalent is included in the final product). The reaction from furfural to mucobromic acid is quite violent and difiicult to control and an expensive bromine recovery system is required to make the procedure at all economical.

We have now found that nitromalonaldehyde 2n To a round-bottom flask with 5 necks containcan be prepared in good yields from the starting mg an efilcient agitator, a, long reflux condenser, material beta-bromo-alpha-chloro-beta-formyla dropping funnel with a long capillary stem, a acrylic acid (mucobromochloric acid). The musub-surface gas feed tube and a thermometer, cobromochloricacid is heated in an aqueous ale e are Charged 6 Parts Of Y b m a d coholic solution in the presence of a nitrite. The 4 7 parts of water and 3 parts of bromine. nitromalonaldehyde is readily recovered as a salt gfie brotrnnie dfistslolvgs rligomrfietilyditn the liquid. from the reaction mixture on cooling. e con en s o e as is ca e 0 65 C. and

It should be noted that the isomeric com- 4 parts of furfural added at such a rate that the pound, the known beta-chloro-alpha-bromot ady fiOW thro h he capillar takes about beta-formylacrylic acid, (mucochlorobromic /2 h u e f u al re ct e o he m ca y acid) gives much lower yields of niaromfilorfialwith bomirehTiie tempertatltretis alfllowedlo dehyde than the new s ar ing ma eria w en reac .an e romines ar s ore ux. s treated with nitrite under the same conditions. soon as the deep red color of the liquid becomes Since nitromalonaldehyde is a relatively unstable ghter, a fast current of chlorine is passed chemical, it is preferably isolated as a salt. Furthrough and thetempe at p at thermore, because it reacts efficiently with guaniby external cooling. The flow of furfural and glue itstyields tcan beh converciiientlty fassaygd chlorine sflguld b; ailgl gfillll th; 3:10: 1:3 by

rough he reac ion wi guani ine o orm welg en a ou wos o e ur ura amin -5-nit yrimidine is added, large quantities of hydrogen chloride to- The present reaction is preferably carried out s th r w th s m carb n d xid s p thr u h at a temperature within the range of c. to h condenser r ms som bromine vapors about 65 C. The aqueous alcoholic solution may Egg gfig zg gggfi swg fi i g g f i gfi g figf fifi gfi gjfg i fi fi ethane furoaltils 11;, the-cltilorine1 culrrent isdcut in half an e empera ure s ow y raise to 95 C. k the abqve. reactlon We prefer to use an al When about 90% of the theoretically needed all metal nitrite. However, we can also use an chlorine is used, it is stopped and the light yellow alkaline earth metal nitrite. The first product 1i quid slowly cooled to 5 C. The slurry of alobtameq IS the Salt. mtromalopaldenyde most white crystals is filtered and washed with responding to the nitrite used WhlCh can be c a smal1 quantity of ice water. Yield, 90-94% of verted to nitromalonaldehyde by neutralization. theory of mucobromochloric acid The starting material beta-bromo-alpha- A solution of 484 parts of sodium nitrite in 600 0111010"betwformylacryhc acld a new @0111- parts of water and 80 parts of methanol is heated pound which is described and claimed in a cot 50 c T thi th i slowly added t 5 pending application, Serial Number 164,851 filed C., with cooling, one half of a solution of 427 May 27, 1950, now Patent Number 2,588,852. A parts of mucobromochloric acid in 240 parts of 4. claims. (01. 260-601) 2 description of its preparation-is also given in the present application. i r

The compound, nitromalonaldehyde, by the present process made, easily accessible in any desired quantity is a. valuable synthetic material. Its reactions with diamines or amidines are most significant yielding nitrated heterocyclic compounds. An example of this is the fact that .ni-. tromalonaldehyde can be reacted withguanidine to produce, 2-aminoe5-nitropyrimidine:, in good overall yields. This latter compound has re-,

cently been found to be highly active in the thera-.

peutic and prophylactic treatment of blackhead disease in turkeys.

The following example illustrates a method of preparing mucobromochloric acid and the use of this intermediate in the preparation of nitromalonaldehyde. All parts are by Weight unless otherwise indicated.

tone and dried at room temperature. The yield is 120 parts, 43%.

Nitromalonaldehyde may be obtained from the above sodium salt by neutralization with an acid, though it is not a very stable compound in the free acidic form. When isolated as the free acidic compound, it is preferably used immediately.

We claim:

hydes which comprises heating to a temperature within the range 40 C. to 65 C. beta-bromo-alpha-chloro-beta-formylacrylic acid with a member of the group consisting of alkali metal nitrites and alkaline earth metal nitrites in the presence of an aqueous lower aliphatic alcoholic solution and recovering said compound therefrom.

3. A method of preparing an alkali metal nitromalonaldehyde which comprises heating to a temperature within the range 40 C. to 65 C. betabromo alpha chloro beta formylacrylic acid with an alkali metal nitrite in the presence of an aqueous lower aliphatic alcoholic solution and recovering said alkali metal nitromalonaldehyde 1. A method of preparing a member of the group consisting of alkali metal nitromalonaldehydes and alkaline earth metal nitromalonaldehydes which comprises heating toa temperature within the range 40 C. to 65C. beta-bromoalpha-chloro-beta-f0rmylacrylic acid with a member of the group consisting of alkali metal nitrites and alkaline earth. metal nitrites in the presence of an aqueous lower aliphatic alcoholic solution and recovering said compound therefrom. a .7

2. A method of preparing a member of the group consisting of alkalimetal nitromalonaldehydes and alkaline earth metal nitromalonaldetherefrom. r

4. A method of preparing sodium nitromalonaldehyde which comprises heating to a temperature within the range C. to C. beta-bromoalpha-chloro-beta-formylacrylic acid with sodium nitrite in an aqueous methanol solution and recovering said sodium nitromalonaldehyde therefrom.

ERWIN KUH. HUGH W. STEWART.

REFERENCES CITED The following references are of record in the file of this patent:

Hill et al., American Chemical Journal, vol. 22, August 1899, No. 2, pp. 89-110. 

1. A METHOD OF PREPARING A MEMBER OF THE GROUP CONSISTING OF ALKALI METAL NITROMALONALDEHYDES AND ALKALINE EARTH METAL NITROMALONALDEHYDES WHICH COMPRISES HEATING TO A TEMPERATURE WITHIN THE RANGE 40* C. TO 65* C. BETA-BROMOALPHA-CHLORO-BETA-FORMYLACRYLIC ACID WITH A MEMBER OF THE GROUP CONSISTING OF ALKALI METAL NITRITES AND ALKALINE EARTH NITRITES IN THE PRESENCE OF AN AQUEOUS LOWER ALIPHATIC ALCOHOLIC SOLUTION AND RECOVERING SAID COMPOUND THEREFROM. 